The primary objective of the Pathology Core for this P01 is to facilitate the discovery and validation of novel targets and therapies for melanoma. To test the therapeutic efficacy of targeted therapies, it is essential to conduct well-planned research using state-of-the art preclinical models; these include patient-derived xenografts (PDXs), transgenic Tyr:creERT2, BRAF[CA/+], [ca/+], PTEN[lox/lox] melanoma mice, and syngeneic models using melanoma cell lines from the mice. As over 1000 patients with melanoma are seen and treated at University of Pennsylvania Health system per year, the Pathology Core is well equipped to provide fresh melanoma tissues to the Cell Biology Core to generate PDXs. Standardized procedures for procurement, processing, storage, quality control, histopathologic evaluation and distribution of samples will ensure optimal utilization and distribution of limited tissue samples to P01 projects. In addition to human samples, the pathology core will serve as a central repository for all mouse tissue generated by this P. The Pathology Core will provide technical support for developing and performing tissue-based assays and the core pathologist will provide expert pathological assistance in the interpretation of histological and immunostaining data. Centralized tissue repository, tissue processing, result acquisition and data interpretation will enable more collaboration across projects and allow new paths of research to emerge. The Core is led by a senior dermatopathologist with extensive experience in translational and laboratory investigation. The Pathology Core will interact with other P01 Cores and other core facilities at Penn and Wistar to support P01 projects. This coordination will allow the P01 investigators to most efficiently perform tissue-based research to find new therapeutic targets as well as to evaluate new combination therapies. In addition to tailoring services to the needs of each project, the central coordination and analysis of tissue will be time- and cost-effective.